Studies have been actively conducted on drug delivery systems (DDS) for the purpose of efficiently delivering drugs to desired sites and avoiding side effects. Among them, a percutaneous absorption system wherein the skin is the application site of a drug, has attracted an attention in recent years. The merit of this system include .vertline.=@ it is thereby possible to avoid the first-pass effect at the liver, .vertline.=A the percutaneous penetration rate of the drug can be controlled so that a long active constant drug level can be maintained, .vertline.=B the administration is not influenced by foods or vomiting, .vertline.=C the administration can easily be adjusted, and .vertline.=D the drug can be administered in the vicinity of the desired site. However, it still has drawbacks such that .vertline.=@ the application is limited to a drug, the dose of which is relatively small, .vertline.=A useful drugs are relatively limited, .vertline.=B there is a possibility that deterioration of the keratin layer or a skin allergy reaction is thereby promoted, and .vertline.=C no rapid action can be expected. Under these circumstances, a combined use of a percutaneous absorption-promoting agent is being studied to overcome such drawbacks.
For example, it has been pointed out in Journal of Controlled Release, Vol. 25, pp. 1-22 (1993) that a variety of low-molecular-weight compounds are effective as percutaneous absorption-promoting agents, with describing abstracts of patents with respect to dimethylsulfoxide, 1-alkylpyrrolidone derivatives, 1-dodecylazacycloheptan-2-on, and the like. The present inventors have proposed, as percutaneous absorption-promoting agents having low toxicity and irritation to the skin, polymeric compounds such as a polymer containing a benzalkonium salt in its side chain (Journal of Controlled Release, Vol. 13. pp.63-71 (1990)), a polymer containing a pyridinium salt in its side chain (Polymer, Vol. 32, No. 11, 2106-2111 (1991)), a polyorganosiloxane containing a N-methylpyridinium salt in its one terminal (Polymer, Vol. 33, No. 10, 2203-2207 (1992)), and a polyorganosiloxane containing a pyridinium or an ammonium salt in its one terminal (EP-0484857A, U.S. Pat. No. 5,200,488).
Among the above promoting agents, however, particularly low-molecular-weight compounds such as dimethylsulfoxide, 1-alkylpyrrolidone derivatives and 1-dodecylazacycloheptan-2-on, had problems at practical application in that they have a toxicity or irritation toward a skin. On the other hand, all the above polymeric compounds proposed by the present inventors exhibited excellent promoting action accompanied with low toxicity and low irritation toward a skin, since they do not penetrate into the interior of the skin owing to the polymeric nature. Especially, the polyorganosiloxane containing a pyridinium or an ammonium salt at its one terminal comprises a polysiloxane chain which is inactive to a living body, and thus its toxicity is very low. However, these conventional polysiloxane type promoting agents have a problem that they are extremely effective for the percutaneous absorption of hydrophobic drugs, but the promoting effect reduces by half in the case of hydrophilic drugs. Therefore, these promoting agents are only applicable to limited drugs.